Recently the distribution of polybrominated diphenyl ethers (PBDE analogs) - the methoxylated and hydroxylated derivatives (MeO-BDE and OH-BDE) and polybrominated dibenzo-p-dioxins (PBDDs)- as well as congeners of the halogenated methyl bipyrroles (MBP) and dimethyl bipyrroles (DMBP) have been examined in a variety of wildlife and humans, where they can often be present at higher concentrations than anthropogenic pollutants. Like anthropogenic pollutants they also bioaccumulate, seem to biomagnify, and toxicity has been demonstrated for at least a subset! However, systematic studies aimed at linking the distribution of HOCs present in apex marine predators to potential source environments through examination of prey and primary producers (a focus of PI and P2) are rare. In this proposal, Aluwihare and Hoh build on an existing collaboration to combine a non-targeted analytical method with a food web-based research approach to assess sources and fates of the entire suite of HOCs in the Southern California Bight Region. In the initial phase of this project the relatively high concentration and unlimited sample size represented by stranded marine mammals will be leveraged to identify and definitively characterize the suite of HOCs (> 200) bioaccumulating in wildlife. This non-targeted approach is facilitated by a novel application of comprehensive wo-dimensional gas chromatography with time- of-flight mass spectrometry (GCxGC/TOF-MS), and relies on collaboration with NOAA and the Southern California Coastal Water Resources Project (SCCWRP). Discovery of new compounds identified by the non-targeted method, will be aided by a variety of authentic standards provided for us by PI and P2. To definitively identify HOC contributions from marine biogenic sources a compound specific radiocarbon and stable isotope approach will also be applied. A recently designed 2D preparative GC will make this research possible. To further establish source, collaborations with PI and P2 will screen a variety of habitat specific primary producers, lower trophic level organisms and pure bacterial cultures for their ability to make HOCs of interest. These major areas of research are tightly integrated with the Analytical Core. To assess human exposure, relevant HOCs will be examined in breast milk samples, and epidemiological investigations will assist in the interpretation of these results with respect to participants' seafood consumption habits. This work will be carried out in collaboration with Christina Chambers, Michelle Leff and Jae Kim (all at UCSD), These data will further inform a study design to examine HOC distributions in relevant seafood products available to consumers. The exposure studies are planned to ultimately assess HOC dietary intake by age and sex from food consumption, and will be done in collaboration with Melbourne Hovell and Jenny Quintana (SDSU). A final component, headed by Kristin Pangallo (Colgate) will begin to interrogate the toxicity of a subset of natural HOCs synthesized and/or isolated by PI and P2. Delineating sources and fates of marine natural HOCs with respect to human health will better inform fisheries management and aquaculture practices, assist with quantifying risks associated with diet, and help to design relevant multiple exposure studies with respect to HOC toxicity.